This Phase 3 study evaluated telaprevir (T) in combination with pegylated-IFN alfa-2a (P) and ribavirin (R) in well-characterised G1 prior-PR treatment failure patients including prior PR non-responders (null and partial) and relapsers.
Method
REALIZE was a randomised, international, multicentre, double-blind, placebo-controlled trial evaluating efficacy, safety and tolerability of T (750 mg q8 h) plus P (180μg/w) and R (1000–1200 mg/d) compared with PR alone. The treatment arms (randomised 2:2:1, stratified by viral load and prior response) were: 12-weeks T/PR, followed by 36-weeks PR (T12PR48); 4-weeks PR followed by 12 weeks T/PR (T delayed start, DS), then 32-weeks PR (T12(DS)/PR48); 48-weeks PR (Pbo/PR48). The primary objective was efficacy of the T/PR arms in non-responders and relapsers. Secondary objectives included evaluation of T DS and efficacy in prior-null and -partial responders. HCV RNA was quantified using COBAS TaqManÆ v2.0 assay (LLOQ=25 IU/ml).
Results
833 patients were screened, and 662 treated. 70% of patients were male, 93% Caucasian, 26% had cirrhosis, and 89% had baseline HCV RNA ≥800 000 IU/ml. AEs reported more frequently in T arms were rash, pruritus, diarrhoea, anorectal disorders and anaemia. 13% of T/PR patients had premature discontinuation (D/C) of T due to AEs: rash (4%) and anaemia (3%) were the most common AEs leading to T D/C.
Conclusion
T/PR SVR was significantly superior to PR in all prior-treatment failure populations including null- and partial-responders. A telaprevir delayed start did not have a significant impact on SVR rates. Safety profile of T/PR was consistent with that observed in treatment naive subjects.
Methods In this analysis, patients with a virologic rebound were defined as those who showed a virologic response at earlier time-points but rebounded to >50 copies/ml in the DUET week 48 dataset. Phenotyping and genotyping at baseline and end-point were performed with the AntivirogramTM and Virco® TYPE HIV-1 assays, respectively, if viral load (VL) was >1000 copies/ml. Emerging mutations were those present at end-point (i.e. the last available resistance test on treatment) but not at baseline. Patients who discontinued the trial for non-virologic reasons were excluded.
Summary. To study the correlation between total Hepatitis C virus (HCV) Core antigen (Ag) and HCV‐RNA, and to assess the proficiency of HCV Core Ag testing in monitoring and predicting virologic response during and after pegylated interferon (PEG‐IFN) and ribavirin combination therapy. A total of 307 samples from treated and untreated patients were used to assess the correlation between the total HCV Core Ag test and quantitative HCV‐RNA assays (Superquant, and Quantiplex branched DNA 2.0 assay). Twenty‐four patients received combination therapy for 48 weeks. Blood samples were collected at day 0, and week 2, 4, 12, 24, 48 and 72 for virologic evaluation. A linear relation exists between total HCV Core Ag and HCV‐RNA levels. At 3 months the positive predictive value (PPV) of response to therapy was 100% with either HCV Core Ag or HCV‐RNA. For HCV Core Ag the negative predictive value (NPV) was 100% whereas for HCV‐RNA the NPV was 80% ( P > 0.05). At month 1, the PPV was 95% and 100% when determined by HCV Core Ag and HCV‐RNA, respectively. The NPV value was 100% for HCV Core Ag and 33% for HCV‐RNA ( P = 0.005). HCV Core Ag quantification could be useful in clinical practice to predict a sustained virological response early during therapy (4 weeks), reaching an optimal performance at month 3. The determination of total HCV Core Ag levels in serum, constitutes an accurate and reliable alternative to HCV‐RNA for monitoring and predicting treatment outcome in patients receiving PEG‐IFN/Ribavirin combination therapy.
